Staphylococcal Enterotoxin B (SEB), classified as a superantigen (SAg) and a category B biological agent, is one of the causes of debilitating Toxic Shock Syndrome, characterized by systemic inflammation, multiorgan damage and vascular collapse. The deleterious effects of SAgs are mediated by the synthesis of copious amounts of inflammatory cytokines. On a cellular level, intracellular signaling pathways activated by SEB-evoked inflammatory cytokines circumvent physiologic regulatory mechanisms that limit cellular responses to inflammation. Suppressors of Cytokine Signaling (SOCS) proteins attenuate pro-inflammatory intracellular signaling. They inhibit kinase activity of cytokine receptor-activated JAKs, or interfere with binding of STATs to activated cytokine receptors, thereby preventing excessive inflammation. Apparently, SEB-induced signaling overrides inhibitory activity of SOCS-1 to prolong injurious cytokine production. Therefore, my proposed research seeks to: 1) characterize SEB-influenced regulation of SOCS 1 effector functions; and 2) examine efficacy of full-length and truncated recombinant Cell-Penetrating SOCS-1 proteins in complementing activity of endogenous SOCS-1 to attenuate SEB-induced toxicosis.